The present application of configurational statistics to model nucleic acids or polynucleotides provides an essential first step in relating the subtle features of chemical architecture to the unique physical and biological properties of these macromolecules. Through a combination of semiempirical energy calculations and statistical mechanical analyses it is possible both to elucidate details of nucleic acid conformation and also to provide a rational understanding of observed experimental phenomena. A first objective of these studies is to understand the unique structural role of the base sequences comprising the nucleic acid chain. A second goal is to comprehend the specific interactions of nucleic acids with other molecular species including small aromatic drugs and dyes, simple antibiotics, and model proteins. The computations not only may supply information useful in predicting the secondary structure of polynucleotides in immense supramolecular structures such as viruses, chromatin, certain DNA-RNA hybrids, and circular DNA but also may provide a molecular basis for understanding the remarkably accurate recognition of nucleic acid sequences by various site specific agents. In addition, it is hoped that the theoretical analyses of nucleic acid conformations, properties, and interactions will anticipate problems of potential interest to experimental investigators.